Experimental and Therapeutic Medicine
·
2019
·Vol. 17
·期 5
·3891-3898
·
IF 1.448
Yuan‑Jun Xia,Wang Wei,Hong Xia,Qing‑Shui Ying,Xiang Yu,Li‑Hua Li,Jian‑Hua Wang,Ying Zhang
In the present study, the effect of recombinant human bone morphogenetic protein‑2 (rhBMP‑2) delivered by chitosan (CS) microspheres on ectopic osteogenesis was investigated in a rat model. rhBMP‑2‑loaded CS microspheres and blank CS microspheres were prepared. A total of 24 male Sprague Dawley rats were divided into 4 groups with 6 rats in each group: The CS/rhBMP‑2 group, the rhBMP‑2 group, in which rhBMP‑2 was directly implanted (rhBMP‑2 dose in either group, 1 mg), the CS blank group and the control group. X‑ray was performed at 4 weeks after ectopic osteogenesis surgery and micro‑computed tomography (CT) examination was scheduled at 1, 2, 3 and 4 weeks after the surgery to determine ectopic osteogenesis in the different groups. Histological analysis, and determination of alkaline phosphatase (ALP) activity and calcium content were also performed. The mean diameter of the osteoid tissues was 1.1±0.3 cm (range, 0.8‑1.4 cm) in the CS/rhBMP‑2 group, which was significantly bigger than that in the rhBMP‑2 group (0.3±0.1 cm; range, 0.1‑0.4 cm) at 4 weeks after the surgery. X‑ray analysis and micro‑CT scan indicated that the area of high‑density tissues and the radionuclide intensity, as well as bone volume in the 3‑dimensional reconstruction were greatest in the CS/rhBMP‑2 group, followed by those in the rhBMP‑2 group. All parameters, including bone mineral density, tissue mineral density, tissue mineral content and bone volume fraction, were significantly higher in the CS/rhBMP‑2 group at 3 and 4 weeks after the surgery, compared with those in the rhBMP‑2 group. The histological analysis, ALP activity analysis and determination of calcium content revealed that the CS/rhBMP‑2 system had the greatest ability to induce osteoblast differentiation. In conclusion, the CS/rhBMP‑2 microsphere delivery system significantly enhanced the induction and promotion effects of rhBMP‑2 regarding ectopic osteogenesis. The present study enhances the basic data available for future application of the CS/rhBMP‑2 microspheres delivery system and provides a deeper understanding of the role of BMP‑2 in bone regeneration.
研究领域:
生物材料
·
骨再生
·
组织工程
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Mofei Han,Kaiqi Tang,Zhenhua Chen
Periodontitis, as a chronic inflammatory oral disease, is the primary cause of tooth loss. The oxidative stress microenvironment of periodontitis causes damage of both osteoblasts’ mitochondrion and periodontal tissue. Natural extracts with antioxidant properties, including resveratrol (RSV), have been reported in regulating oxidative stress microenvironment, however, the controlled release of them in periodontal tissue is still a challenge. Herein, a smart photothermal-responsive gold nanocages hydrogel (RSV-Au@H) was constructed for the treatment of periodontitis by controlling the release of resveratrol. Under the near-infrared (NIR) light irradiation for 5 min, RSV-Au@H could be heated to 45.8 ℃ due to the good photothermal effect of Au nanocages encapsulated in the hydrogel. This NIR stimulated photothermal effect of RSV-Au@H could control the release of RSV. Molecular biology indicated that RSV-Au@H could scavenge ROS with 42 % efficiency. Transmission electron microscopy (TEM) showed a significant improvement in osteoblasts mitochondrial morphology. Micro-CT scanning revealed that RSV-Au@H reduced the distance between cemento-enamel junction and alveolar bone crest (CEJ-ABC) by up to 55 % and increased bone volume fraction by about 48 %. These results suggested that this multifunctional nanoplatform with NIR controlled release of RSV might be a new therapeutic strategy for periodontitis.
研究领域:
牙科学
·
纳米技术
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药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2024
·
IF 4.2
Bin Wang,Wei Wang,Jingyu Li,Jianjun Li
The molecular mechanism underlying the promotion of fracture healing by mechanical stimuli remains unclear. The present study aimed to investigate the role of zinc finger protein 36 like 2 (ZFP36L2)-histone deacetylase 1 (HDAC1) axis on the osteogenic responses to moderate mechanical stimulation. Appropriate stimulation of fluid shear stress (FSS) was performed on MC3T3-E1 cells transduced with ZFP36L2 and HDAC1 recombinant adenoviruses, aiming to validate the influence of mechanical stress on the expression of ZFP36L2-HDAC1 and the osteogenic differentiation and mineralization. The results showed that moderate FSS stimulation significantly upregulated the expression of ZFP36L2 in MC3T3-E1 cells ( p < 0.01). The overexpression of ZFP36L1 markedly enhanced the levels of osteogenic differentiation markers, including bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), Osterix, and collagen type I alpha 1 (COL1A1) ( p < 0.01). ZFP36L2 accelerated the degradation of HDAC1 by specifically binding to its 3’ UTR region, thereby fulfilling its function at the post-transcriptional regulatory gene level and promoting the osteogenic differentiation and mineralization fate of cells. Mechanical unloading notably diminished/elevated the expression of ZFP36L2/HDAC1, decreased bone mineral density and bone volume fraction, hindered the release of osteogenic-related factors and vascular endothelial growth factor in callus tissue ( p < 0.01), and was detrimental to fracture healing. Collectively, proper stress stimulation plays a crucial role in facilitating osteogenesis through the promotion of ZFP36L2 and subsequent degradation of HDAC1. Targeting ZFP36L2-HDAC1 axis may provide promising insights to enhance bone defect healing.
研究领域:
骨科
·
分子生物学
·
细胞生物学
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生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2024
·
IF 4.5
Zhiguang Chen,Qi Zhao,Lianghong Chen,Songlan Gao,Lingshuai Meng,Yingjie Liu,Yu Wang,Tiegang Li,Jinqi Xue
Osteogenic differentiation is important for fracture healing. Microfibrial-associated glycoprotein 2 (MAGP2) is found to function as a proangiogenic regulator in bone formation; however, its role in osteogenic differentiation during bone repair is not clear. Here, a mouse model of critical-sized femur fracture was constructed, and the adenovirus expressing MAGP2 was delivered into the fracture site. Mice with MAGP2 overexpression exhibited increased bone mineral density and bone volume fraction (BV/TV) at Day 14 postfracture. Within 7 days postfracture, overexpression of MAGP2 increased collagen I and II expression at the fracture callus, with increasing chondrogenesis. MAGP2 inhibited collagen II level but elevated collagen I by 14 days following fracture, accompanied by increased endochondral bone formation. In mouse osteoblast precursor MC3T3-E1 cells, MAGP2 treatment elevated the expression of osteoblastic factors (osterix, BGLAP and collagen I) and enhanced ALP activity and mineralization through activating β-catenin signaling after osteogenic induction. Besides, MAGP2 could interact with lipoprotein receptor-related protein 5 (LRP5) and upregulated its expression. Promotion of osteogenic differentiation and β-catenin activation mediated by MAGP2 was partially reversed by LRP5 knockdown. Interestingly, β-catenin/transcription factor 4 (TCF4) increased MAGP2 expression probably by binding to MAGP2 promoter. These findings suggest that MAGP2 may interact with β-catenin/TCF4 to enhance β-catenin/TCF4's function and activate LRP5-activated β-catenin signaling pathway, thus promoting osteogenic differentiation for fracture repair. mRNA sequencing identified the potential targets of MAGP2, providing novel insights into MAGP2 function and the directions for future research.
研究领域:
骨骼生物学
·
骨科
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yuna Shang,Qingrun Zhu,Jiaming Ding,Liang Zhao,Fan Zhang,Jiayi Lu,Yinyin Feng,Jiayu Wang,Zhixue Liu,Mingjie Kuang,Chunju Li
Bioactive peptides play a crucial role in the field of regenerative medicine and tissue engineering. However, their application in vivo and clinic is hindered by their poor stability, short half-life, and low retention rate. Herein, we propose a novel strategy for encapsulating bioactive peptides using giant macrocycles. Platelet-derived growth factor (PDGF) bioactive mimicking peptide Nap-FFGVRKKP ( P ) was selected as the representative of a bioactive peptide. Quaterphen[4]arene ( 4 ) exhibited extensive host-guest complexation with P , and the binding constant was (1.16 ± 0.10) × 10 7 M −1 . In vitro cell experiments confirmed that P + 4 could promote the proliferation of BMSCs by 2.27 times. Even with the addition of the inhibitor dexamethasone (Dex), P + 4 was still able to save 76.94% of the cells in the control group. Compared to the Dex group, the bone mass of the mice with osteoporosis in the P + 4 group was significantly increased. The mean trabecular thickness (Tb.Th) increased by 17.03%, and the trabecular bone volume fraction (BV/TV) values increased by 40.55%. This supramolecular bioactive peptide delivery strategy provides a general approach for delivering bioactive peptides and opens up new opportunities for the development of peptide-based drugs.
研究领域:
再生医学
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组织工程
·
药学
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骨骼生物学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2020
·
IF 7.635
Cijun Shuai,Yun Cheng,Wenjing Yang,Pei Feng,Youwen Yang,Chongxian He,Fangwei Qi,Shuping Peng
Most of the existing scaffolds do not provide physical stimulation to cells in scaffold-guided bone regeneration. In this work, a superparamagnetic scaffold was fabricated using selective laser sintering with polyglycolic acid as matrix and Fe 3 O 4 nanoparticles as internal magnetic source. Additionally, a self-developed external static magnetic field (SMF) was used to provide external magnetic source. In this case, the magnetic moment of the Fe 3 O 4 nanoparticles rearranged along the direction of SMF, thereby generating a locally enhanced magnetic field. The enhanced magnetic field might directly stimulate cell surface receptors and activate downstream signaling pathways. As a consequence, the human umbilical cord-derived mesenchymal stem cells cultivated in the scaffold exhibited significantly enhanced gene expression of alkaline phosphatase , osteocalcin, type I collagen and runt-related transcription factor-2. In vivo tests revealed that the bone regeneration was accelerated with bone mineral density (with SMF: 515 ± 50 mg/cc, without SMF: 326 ± 15 mg/cc), percentage of bone volume/tissue volume (with SMF: 92 ± 3.5%, without SMF: 73 ± 5.2%) and new bone area fraction (with SMF: 86 ± 2.2%, without SMF: 70 ± 1.6%) after 8 weeks' implantation. The biodistribution and serum biochemistry analysis demonstrated that superparamagnetic scaffold possessed favorable biosafety.
研究领域:
生物材料
·
组织工程
·
再生医学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 46
·9639-9653
·
IF 7.571
Xinyuan Yuan,Teliang Lu,Fupo He,Tingting Wu,Xiaolan Wang,Jiandong Ye
Biomaterials in combination with multiple bioactive ions could create a favorable microenvironment for bone remolding. Herein, zinc silicate/β-tricalcium phosphate (ZS/β-TCP) composite ceramic scaffolds with different amounts of ZS (5, 10, and 15 wt%) were constructed using a three-dimensional fiber deposition (3DF) technique. The physicochemical, osteogenic and angiogenic properties of these interconnected macroporous scaffolds were investigated systematically. Simultaneously, GeneChip, alkaline phosphatase (ALP), western blot (WB) and polymerase chain reaction (PCR) were utilized to elucidate the underlying mechanism of the enhancement in osteogenic differentiation. The results showed that the incorporation of ZS significantly improved the mechanical performance by more than 5 fold in comparison with the β-TCP ceramic scaffold (4.79 ± 0.99 MPa). The ZS modified β-TCP scaffolds greatly supported the cytoactivity, adhesion, proliferation of mouse bone marrow mesenchymal stem cells (mBMSCs) and human umbilical vein endothelial cells (HUVECs). The expression levels of osteogenic genes and proteins as well as angiogenic genes were markedly upregulated by the sustained release of bioactive ions (mainly Si and Zn) from the composite scaffolds. The 10ZS/β-TCP demonstrated the best overall performance in vitro. Moreover, the 10ZS/β-TCP displayed a high bone volume fraction, bone maturity and angiogenesis after implantation in the rat skull defects for 6 weeks. It was further verified that ZS/β-TCP scaffolds stimulated the osteogenic differentiation of mBMSCs by activating the p38 signaling pathway directly. The 10ZS/β-TCP ceramic scaffold holds great potential for the fast repair of bone defects, and deep understanding of the mechanism will facilitate the formulation of new strategies for bone repair.
研究领域:
生物材料
·
组织工程
·
骨再生
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Eunshinae Cho,Yi Qiao,Changan Chen,Junjie Xu,Jiangyu Cai,Yamin Li,Jinzhong Zhao
Features of black phosphorous (BP) nano sheets such as enhancing mineralization and reducing cytotoxicity in bone regeneration field have been reported. Thermo-responsive FHE hydrogel (mainly composed of oxidized hyaluronic acid (OHA), poly-ε-L-lysine (ε-EPL) and F127) also showed a desired outcome in skin regeneration due to its stability and antibacterial benefits. This study investigated the application of BP-FHE hydrogel in anterior cruciate ligament reconstruction (ACLR) both in in vitro and in vivo , and addressed its effects on tendon and bone healing. This BP-FHE hydrogel is expected to bring the benefits of both components (thermo-sensitivity, induced osteogenesis and easy delivery) to optimize the clinical application of ACLR and enhance the recovery. Our in vitro results confirmed the potential role of BP-FHE via significantly increased rBMSC attachment, proliferation and osteogenic differentiation with ARS and PCR analysis. Moreover, In vivo results indicated that BP-FHE hydrogels can successfully optimize the recovery of ACLR through enhancing osteogenesis and improving the integration of tendon and bone interface. Further results of Biomechanical testing and Micro-CT analysis [bone tunnel area (mm2) and bone volume/total volume (%)] demonstrated that BP can indeed accelerate bone ingrowth. Additionally, histological staining (H&E, Masson and Safranin O/fast green) and immunohistochemical analysis (COL I, COL III and BMP-2) strongly supported the ability of BP to promote tendon-bone healing after ACLR in murine animal models.
研究领域:
组织工程
·
再生医学
·
骨科手术
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）